Biomedical subjects

M Ikeda

Publications and source records attributed to M Ikeda.

At least 127 records · Page 7Linked to original sources

PubMed2001

First successful molecular design of an artificial Lewis oligosaccharide binding system utilizing positive homotropic allosterism.

We have designed phenylboronic acid group appended Ce(IV) bis(porphyrinate) double decker 1 and meso-meso linked porphyrin 2, useful for the allosteric binding of biologically important saccharides, Lewis oligosaccharides. Compound 1 binds Lewis oligosaccharides in aqueous media because of the boronic acid-diol interaction, but the complexation event can occur only above the critical concentrations because of the sigmoidal [oligosaccharide] versus [complex] isotherm. Compound 1 has a sufficiently high affinity with Lewis oligosaccharides (K = 10(5)-10(6) M(-2)) with Hill coefficients n of 1.8-2.0, and Lewis(X) series and Lewis(a) series give opposite, symmetrical CD spectra. This is the first example of efficient binding of Lewis oligosaccharides to the artificial receptor, which has become possible by positive homotropic allosterism.

Carbohydrate Conformation↗

PubMed2001

Rudimentary TCR signaling triggers default IL-10 secretion by human Th1 cells.

Understanding the process of inducing T cell activation has been hampered by the complex interactions between APC and inflammatory Th1 cells. To dissociate Ag-specific signaling through the TCR from costimulatory signaling, rTCR ligands (RTL) containing the alpha1 and beta1 domains of HLA-DR2b (DRA*0101:DRB1*1501) covalently linked with either the myelin basic protein peptide 85-99 (RTL303) or CABL-b3a2 (RTL311) peptides were constructed to provide a minimal ligand for peptide-specific TCRs. When incubated with peptide-specific Th1 cell clones in the absence of APC or costimulatory molecules, only the cognate RTL induced partial activation through the TCR. This partial activation included rapid TCR zeta-chain phosphorylation, calcium mobilization, and reduced extracellular signal-related kinase activity, as well as IL-10 production, but not proliferation or other obvious phenotypic changes. On restimulation with APC/peptide, the RTL-pretreated Th1 clones had reduced proliferation and secreted less IFN-gamma; IL-10 production persisted. These findings reveal for the first time the rudimentary signaling pattern delivered by initial engagement of the external TCR interface, which is further supplemented by coactivation molecules. Activation with RTLs provides a novel strategy for generating autoantigen-specific bystander suppression useful for treatment of complex autoimmune diseases.

Calcium Signaling↗

PubMed2001

Stability of amorphous indomethacin compounded with silica.

The stability of indomethacin (IM) compounded with SiO(2) either by co-grinding or by melt-quenching was examined by recrystallization kinetics under the conditions 30 degrees C and 11% relative humidity. A decrease of the recrystallization rate with and without an appreciable induction period was observed in both compounds. Higher stability of amorphous IM compounded with SiO(2) was attained by prolonged co-grinding than by melt-quenching. This was explained by the stronger chemical interaction at the interface between IM and SiO(2) by co-grinding, as revealed by (29)Si and (13)C solid state NMR. Incomplete co-grinding with the rest of the crystalline state, however, made the amorphous state appreciably unstable, since the remaining crystallites serve as seeds for recrystallization.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2001

Increased prevalence of vascular dementia in Japan: a community-based epidemiological study.

BACKGROUND AND OBJECTIVE: It has been suggested that there is a major difference in the ratio of AD to vascular dementia (VaD) between Japan and Western countries. To determine the type-specific prevalence of dementia in community-dwelling elderly from the Japanese community of Nakayama, all patients with dementing illness underwent a CT scan. METHODS: A door-to-door three-phase population survey was carried out on all persons aged 65 years and older residing at home on the prevalence day (January 1, 1997). The ascertainment of cases was made between January 1997 and March 1998. The study included a psychiatric interview; physical, neurologic, and neuropsychologic examinations; comprehensive laboratory tests; and cranial CT. A public health nurse also interviewed a person close to each subject. Dementia was defined according to the Diagnostic and Statistical Manual of Mental Disorders, third edition-revised, criteria, AD according to the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association, and VaD according to Diagnostic and Statistical Manual of Mental Disorders, fourth edition, combined with information from the patient's neurologic history and CT scanning. RESULTS: Of 1438 inhabitants, 1162 (81.0%) completed the protocol. The prevalence of dementia was 4.8%. Of the 60 subjects with dementia, 35% had AD, 47% had VaD, and 17% had dementia resulting from other causes. CONCLUSIONS: The prevalence of dementia was similar to previous reports, but, contrary to results of virtually all studies conducted in developed countries and those recently conducted in Japan, almost half of the cases in the present study appeared to have VaD with neuroradiologic confirmation.

Aged↗

PubMed2001

Phospholipase Cbeta4 and protein kinase Calpha and/or protein kinase CbetaI are involved in the induction of long term depression in cerebellar Purkinje cells.

Activation of the type-1 metabotropic glutamate receptor (mGluR1) signaling pathway in the cerebellum involves activation of phospholipase C (PLC) and protein kinase C (PKC) for the induction of cerebellar long term depression (LTD). The PLC and PKC isoforms that are involved in LTD remain unclear, however. One previous study found no change in LTD in PKCgamma-deficient mice, thus, in the present study, we examined cerebellar LTD in PLCbeta4-deficient mice. Immunohistochemical and Western blot analyses of cerebellum from wild-type mice revealed that PLCbeta1 was expressed weakly and uniformly, PLCbeta2 was not detected, PLCbeta3 was expressed predominantly in caudal cerebellum (lobes 7-10), and PLCbeta4 was expressed uniformly throughout. In PLCbeta4-deficient mice, expression of total PLCbeta, the mGluR1-mediated Ca(2+) response, and LTD induction were greatly reduced in rostral cerebellum (lobes 1-6). Furthermore, we used immunohistochemistry to localize PKCalpha, -betaI, -betaII, and -gamma in mouse cerebellar Purkinje cells during LTD induction. Both PKCalpha and PKCbetaI were found to be translocated to the plasmamembrane under these conditions. Taken together, these results suggest that mGluR1-mediated activation of PLCbeta4 in rostral cerebellar Purkinje cells induced LTD via PKCalpha and/or PKCbetaI.

Animals↗

PubMed2001

Natural infection of wild-born mandrills (Mandrillus sphinx) with two different types of simian immunodeficiency virus.

We found a novel primate lentivirus in mandrill (Mandrillus sphinx). To clarify the evolutionary relationships and transmission patterns of human/simian immunodeficiency virus (HIV/SIV), we screened blood samples from 30 wild-born healthy Cameroonian mandrills. Five (16.7%) of them were seropositive for SIV. Three SIV strains were isolated from the five seropositive mandrills by cocultivation of their peripheral blood mononuclear cells (PBMCs) with PBMCs of rhesus macaques, a human T cell line (M8166), and/or a cynomolgus macaque T cell line (HSC-F). One of the newly isolated SIV strains was intravenously inoculated into two rhesus macaques and resulted in chronic infection. In the SIV-infected macaques at 45 weeks after inoculation, we observed a mild decline in the number of peripheral CD4(+) lymphocytes, lymphadenopathy, and blastic follicular dendritic cells with mild follicular hyperplasia in the peripheral lymph nodes. A phylogenetic analysis based on the pol sequence showed that the newly found SIVs from Cameroonian mandrills did not cluster with SIVmndGB1, which is the former representative strain of SIVmnd. The SIVmnds from Cameroon formed a new, independent lineage that branched before the root of the HIV-1/SIVcpz lineage with 996 of 1000 bootstrap replications. They clustered host specifically, and exhibited about 16.9% diversity at the level of nucleotide sequence among Cameroonian SIVmnd strains. These results indicate that the SIVmnds isolated in Cameroon are a novel type of SIVmnd and have infected Cameroonian mandrills for a long time. We therefore designated the Cameroonian SIVmnd as SIVmnd type 2 and redesignated SIVmndGB1 as SIVmnd type 1. To date, M. sphinx is the only primate species other than humans that is naturally infected with two different types of SIV.

Animals↗

PubMed2001

Molecular cloning and characterization of a steroid receptor-binding regulator of G-protein signaling protein cDNA.

Steroid hormone receptors are composed of six major functional domains, i.e. the A/B domains as the activation function 1 domain (AF-1), domain C as the DNA-binding domain, domain D as a hinge domain and domain E/F as the ligand-dependent transcriptional domain (AF-2). They regulate gene transcription through interactions with various nuclear factors of their domains, such as AF-1 and AF-2. We have insufficient knowledge of the function of the DNA-binding domain (domain C) except for its DNA-binding function or the hinge domain (domain D). Therefore, we attempted to identify factors interacting with the domains by using a yeast two-hybrid system. Domains C and D of estrogen receptor alpha were used as a bait to isolate cDNA clones from a rat ovary cDNA library. We isolated the cDNA clone of a novel steroid receptor-binding protein bearing the regulator of G-protein signaling (RGS) designated as SRB-RGS. The protein repressed the transcriptional activity of estrogen receptor alpha, suggesting cross-talk of steroid hormones and peptide hormones (or growth factors) for signal transductions mediated by SRB-RGS.

Amino Acid Sequence↗

PubMed2001

Alteration of rCBF in Alzheimer's disease patients with delusions of theft.

We investigated the neural substrate of the delusion of theft in patients with Alzheimer's disease (AD). Nine AD patients with only one type of delusion (delusions of theft) and nine age, cognitive function-matched AD patients without any type of delusions were selected from 334 consecutive outpatients of Ehime University Hospital. All subjects underwent (99m)Tc-HMPAO SPECT scanning, and SPECT images were analyzed by Statistical Parametric Mapping (SPM). AD patients with delusions of theft showed significant hypoperfusion in the right medial posterior parietal region compared to patients without delusions. Our data suggest that attention impairment or lack of awareness of illness caused by right parietal dysfunction might play a role in producing the delusion of theft.

Age Factors↗

PubMed2001

Connexin43 suppresses proliferation of osteosarcoma U2OS cells through post-transcriptional regulation of p27.

Many lines of evidence indicate that connexin genes expressing gap junction (GJ) proteins inhibit tumor cell proliferation. However, the precise molecular mechanisms remain unclear. In this study, we show that overexpression of connexin43 (Cx43) suppressed proliferation of human osteosarcoma U2OS cells through inhibition of the cell cycle transition from G1 to S phase. This inhibition was attributed to a significant accumulation of the hypophosphorylated retinoblastoma (Rb) protein, which was causally related to decreases in the kinase activities of cyclin-dependent kinases (CDKs) 2 and 4. Enforced Cx43 expression markedly increased the level of the CDK inhibitor p27. This increase resulted from an increased synthesis and a reduced degradation of the p27 proteins, but not influence of the p27 mRNA. Moreover, we show that the Cx43-modulated GJ function was the main contributor to the elevation in p27 levels, in which cAMP was involved. These data suggest that Cx43 appears to inhibit proliferation of U2OS cells by increasing the levels of p27 proteins via post-transcriptional regulatory mechanisms.

Base Sequence↗

PubMed2001

Antitumor effect of beta2-microglobulin in leukemic cell-bearing mice via apoptosis-inducing activity: activation of caspase-3 and nuclear factor-kappaB.

We have reported previously that beta2-microglobulin (beta2m) induces apoptosis in leukemic cells in vitro, and that an interaction between beta2m and HLA class I antigen induces apoptosis. Here we examined whether beta2m can induce apoptosis in leukemic cells in vivo and whether it has an antitumor effect in tumor-bearing mice. Daily administration of 50 or 250 microg of beta2m induced apoptosis and an antitumor effect on K562 leukemia cell-bearing mice in the same manner as tumor necrosis factor-alpha. In tumor tissues in beta2m-treated mice, both caspase-3 and nuclear factor-kappaB (NF-kappaB) were stained more strongly than in control mice by anti-caspase-3 and anti-NF-kappaB p65/Rel A polyclonal antibodies. We also observed the in vivo immunological effects of beta2m on lymphoid and hematopoietic organs, such as thymus, bone marrow, Peyer's patches, liver, and spleen in normal mice. Using antibodies against caspase-3 and NF-kappaB, immunohistochemical staining showed that no specific tissues were damaged or stained in normal mice. We conclude that beta2m stimulates caspase-3 and NF-kappaB pathways to induce apoptosis, making it a useful approach to a new therapy for leukemia.

Animals↗

PubMed2001

Photoallylation and photoreduction of cyclohexylidenepropanedinitrile by use of allyltrimethylsilane via photoinduced electron transfer: control of the product ratio depending on pK(a) values of additives.

Irradiation of an acetonitrile solution containing cyclohexylidenepropanedinitrile (1) and allyltrimethylsilane (2) in the presence of phenanthrene afforded two kinds of allylated products (3, 4) and a reduction product (5). The product ratio of 3, 4, and 5 dramatically changed depending on the pK(a) values of additives.

Journal Article↗

PubMed2001

Circadian pattern, light responsiveness and localization of rPer1 and rPer2 gene expression in the rat retina.

Circadian expression, light-responsiveness and localization of clock genes, rPer1 and rPer2, were examined in the rat retina under constant darkness. A significant circadian variation was detected in rPer2 transcript levels with a peak at ZT14, but not in the rPer1. A light pulse given after constant darkness of 3 days increased both rPer1 and rPer2 expression phase-dependently, while rPer1 was induced at more times than rPer2. A major site of these gene expression within the retina was the inner nuclear layer. These findings indicate that rPer1 and rPer2 genes play different roles in the generation and regulation of circadian rhythms in the retina from those in the suprachiasmatic nucleus.

Animals↗

PubMed2001

Evaluation of the effects of exercise and a mild hypocaloric diet on cardiovascular risk factors in obese subjects.

A weight reduction program to improve cardiovascular risk factors was implemented in obese subjects. The program consisted of exercise training corresponding to the anaerobic threshold (AT) and a mild hypocaloric diet for 12 weeks. In this program, we evaluated the effects of a combination of exercise training and a diet on cardiovascular risk factors such as obesity, dyslipidemia, and poor exercise performance in obese subjects. In addition, we also evaluated the independent effects of exercise training and dietary modification. For this purpose, we adopted a relative training time and a diet score. A relative training time was calculated as the number of times that the subject performed exercises divided by all of the training sessions scheduled, and the diet score was calculated from information which each subject provided on a self-assessment questionnaire. Twenty three obese subjects (Age: 24-54 years old, 19 men and 4 women, body mass index (BMI) > 26 kg/m2) participated in this study. After the 12-week intervention, the mean reductions in body weight, body mass index and body fat were 4.7 kg, 1.7 kg/m2 and 2.9%, respectively (P < 0.0001). The % change in body weight was significantly associated with the diet score and with the relative training time. The mean reductions in total cholesterol, triglyceride and low density lipoprotein cholesterol were 21 mg/dl (P < 0.002), 34 mg/dl (P < 0.01) and 15.9 mg/dl (P < 0.01), respectively, and the % change in triglyceride was significantly associated with the diet score (P = 0.0056) and tended to correlate with the relative training time (P = 0.0596). Oxygen uptake at AT and at peak exercise were increased from 14.1 +/- 1.6 to 16.0 +/- 3.1 ml/min/kg (P < 0.005) and from 26.3 +/- 4.8 to 28.4 +/- 4.9 ml/min/kg (P < 0.002), respectively. A combination of aerobic exercise and a mild hypocaloric diet significantly contributed not only to weight loss but also to the improvement of dyslipidemia and exercise performance, but either hypocaloric diet or mild exercise independently did less. The diet score and the relative training time were useful for evaluating separately dietary modification and the quantity of exercise.

Adult↗

PubMed2001

A novel mutation lacking the bromodomain of the transcriptional coactivator p300 in the SiHa cervical carcinoma cell line.

The transcriptional coactivator p300, a histone acetyltransferase (HAT), plays key roles in the regulation of cell proliferation and differentiation. p300 is targeted by viral oncoproteins, and mutations of p300, accompanied by inactivation of the second allele, have been reported in certain types of cancers originating in the epithelium. Here, we identified a homozygous p300 deletion of exons 15--18 in the SiHa cervical carcinoma cell line, which results in an in-frame deletion that causes specific loss of the bromodomain, a conserved domain implicated in the regulation of HAT activity. Furthermore, we show that the mutation severely impaired its ability to activate the p21(WAF1/CIP1) promoter in transient reporter assay. These results suggest a critical role for the bromodomain in p300 functions as a tumor-suppressor gene.

Base Sequence↗

PubMed2001

Abeta amyloidosis induces the initial stage of tau accumulation in APP(Sw) mice.

To clarify how Abeta deposits induce secondary tauopathy, the presence of phosphorylated tau, glycogen synthase kinase 3alpha (GSK3alpha), GSK3beta, cyclin-dependent kinase 5 (CDK5), mitogen-activated protein kinase (MAPK) and fyn were examined in the Tg2576 brain showing substantial brain Abeta amyloidosis and behavioral abnormalities. Phosphorylated tau at Ser199, Thr231/Ser235, Ser396 and Ser413 accumulated in the dystrophic neurites of senile plaques. The major kinase for tau phosphorylation was GSK3beta. Smaller contributions of GSK3alpha, CDK5 and MAPK were suggested. Thus, brain Abeta amyloidosis has a potential role in the induction of tauopathy leading to the mental disturbances of Alzheimer's disease.

Alzheimer Disease↗

PubMed2001

Clock gene expressions in the suprachiasmatic nucleus and other areas of the brain during rhythm splitting in CS mice.

The CS mouse is a mutant strain which displays spontaneous splitting in the circadian locomotor rhythm under continuous darkness. To clarify whether the rhythm splitting occurs in the suprachiasmatic nucleus (SCN) where the mammalian circadian clock is located, the circadian rhythmicities of mammalian clock genes, mPer1, mBMAL1 and mClock, were examined in the SCN and cerebral cortex during rhythm splitting. The circadian profiles of the clock genes during rhythm splitting were essentially the same as those observed under unsplit conditions. However, the mPer1 gene expression throughout the day was bimodal in the piriform and cingulate cortices, peaking in correspondence with two split components of behavioral rhythm. These results indicate that the circadian profiles of three clock gene expressions in the SCN are not consistent with the overt circadian locomotor rhythm, suggesting that the site of rhythm splitting is somewhere outside the SCN, or alternatively different subregions or other clock genes in the SCN are involved in rhythm splitting.

ARNTL Transcription Factors↗

PubMed2001

High expression of HLA-A2 on an oral squamous cell carcinoma with down-regulated transporter for antigen presentation.

Using the reverse transcription PCR, we evaluated expression levels of various antigen presentation-related genes, including LMP2, LMP7, MECL-1, PA28alpha, PA28beta, TAP1, TAP2, and tapasin, in two oral squamous cell carcinoma cell lines, HSC5 and HSC7. Expression levels of LMP2, MECL-1, TAP1, and TAP2 transcripts are reduced in both cell lines in comparison with a normal epithelial cell line. Further, HSC5 and HSC7 show diminished expression of LMP7/tapasin, and PA28alpha/beta, respectively. Surface expression of HLA-B alleles is down-regulated in both lines presumably due to low expression of TAP1/2. However, HLA-A2 surface expression is not significantly down-regulated in HSC5 cells, suggesting an involvement of signal-sequence derived peptides in the TAP-independent pathway. The current study would contribute to our understanding of significance of abnormalities in the antigen presentation machinery of oral squamous cell carcinoma, and provide meaningful information in the design of CTL-based tumor vaccines by intra-cellular delivery system.

Antigen Presentation↗

PubMed2001

Prognostic factors in patients with locally advanced pancreatic carcinoma receiving chemoradiotherapy.

BACKGROUND: The combination of radiation therapy and chemotherapy (chemoradiotherapy [CRT]) has been accepted as standard therapy for patients with locally advanced pancreatic carcinoma (PC). This study investigated prognostic factors in patients with locally advanced PC receiving CRT. METHODS: Fifty-five consecutive patients with locally advanced PC, who received concurrent radiotherapy (50.4 grays) and chemotherapy using 5-fluorouracil or cisplatin, were analyzed retrospectively to investigate prognostic factors. RESULTS: Median survival time and overall survival rates at 1 and 2 years were 301 days, 35.1% and 2.4%, respectively. By multivariate analysis using the Cox proportional hazards model, performance status of 0-1 (P < 0.01), absence of regional lymph node swelling (P < 0.01), and serum CA 19-9 level of less than 1000 (P = 0.02) were independent favorable prognostic factors. A prognostic index based on the coefficients of those prognostic factors was used to classify patients into three groups with good, intermediate, and poor prognoses. The median survival times for these three groups were 410, 239, and 143 days, respectively (P < 0.01). CONCLUSIONS: The results may be helpful in predicting life expectancy, determining treatment strategies, and designing future clinical trials.

Adult↗